Apeikon Therapeutics: tackling the side effects of chemotherapy through targeted triggered drug delivery

Written by Charlotte Pugsley, edited by Daniele Guido and Molly Steadman.

“Any disease that could benefit from the local delivery of a high drug concentration could potentially benefit from this technology.” – Dr. Moh Tadayyon

Apeikónisi, the Greek word for ‘imaging’, is where Apeikon Therapeutics took inspiration for its name.  Their revolutionary image-guided 3T technology is being developed to specifically deliver and release chemotherapy drugs to the tumour site. Apeikon Therapeutics are taking part in the SEC Innovators Club in 2021, so we took the opportunity to sit down with the co-founders to learn more about their technology and the challenges they have faced when ‘spinning-out’ a company from academia.

Despite only having entered the start-up world in December 2020, the co-founders Dr Maya Thanou and Dr Moh Tadayyon of Apeikon Therapeutics are far from inexperienced. Dr Thanou, a Reader at Kings College London, has previously worked at Imperial College London and Cardiff University. Throughout her career Dr Thanou has been an innovator, with nine patents to her name. Alongside Maya is Dr Moh Tadayyon, who joined the pharmaceutical industry (GlaxoSmithKline) in 1995. Moh brings a unique blend of experience to Apeikon Therapeutics across the pharma ‘value chain’ from drug discovery to commercial strategy.  Whilst at Boehringer-Ingelheim, Moh co-led the discovery, patenting and profiling of a number of therapeutics that progressed to the clinic, including linagliptin that is now a successful antidiabetic agent.  Dr Tadayyon is passionate about bringing new therapies to the clinic to improve the lives of patients.  Moh says this is what drew him to Dr Thanou’s research during a Knowledge Transfer Partnership meeting back in 2016. After validating the concept and evaluating the commercial potential, Dr Tadayyon and Dr Thanou were convinced of the market and clinical need and became co-founders of Apeikon Therapeutics.

The Problems with Chemotherapy

Most of us will be aware of the common side effects of chemotherapy drugs used to combat cancer, such as: hair loss, fatigue and nausea (1). However, the list of potential side effects is in fact more severe and includes complications such as anaemia, susceptibility to infection, internal bleeding and problems with the peripheral nervous system. The side effects caused by chemotherapy are due to the drugs being unspecific and their systemic exposure (2). It is these issues with most anticancer drugs that is the driving force behind the novel work being undertaken by Apeikon.

The 3T Technology

Targeted, triggered treatment – these are the three key words that make up the ‘3T’ technology of Apeikon Therapeutics. The technology will change the way that doctors are able to deliver chemotherapy drugs to patients by delivering drugs at high doses, only at the specific site of the tumour. In doing so, side effects caused by the uniform distribution of drugs throughout the body will be hugely reduced.

Lipid drug carriers, such as the liposomes shown in Figure 2, are made of lipid molecules that arrange into spherical vesicles with a bilayer membrane that is very similar to the membranes of mammalian cells. Liposomes have been used to deliver numerous drugs already, and most recently, the COVID-19 vaccine (3) by carrying their cargo within the core of the vesicles.

Apeikon Therapeutics uses liposomes to carry chemotherapy drugs for delivery. As suggested by their name (apeikónisi), imaging is an important part of the 3T technology, and Apeikon Therapeutics uses magnetic resonance imaging (MRI) labels, coupled to the lipids, to act as the ‘contrast agent’ when imaging the body with MRI. These labels are commonly used when a patient goes for a MRI scan, which is a non-invasive technique used to obtain images of tissues inside the body (4).

The MRI-labelled liposomes, with the chemotherapy drugs encapsulated, can be injected and travel with the blood around the body. With the MRI imaging capability, the tumour is imaged and focused ultrasound (FUS) is directed onto the tumour site. FUS concentrates in a small, precise volume of 1 mm in diameter and about 10 mm in length, and the energy of several ultrasound elements temporarily increase the temperature of the target location to 42 °C. The local hyperthermia (temperature increase) causes the liposome porosity to increase, inducing the release of the chemotherapy drug only at the tumour site. The drug release is rapid and provides a high dose, due to the large amount of drug that can be encapsulated within the liposomes. The liposomes elsewhere in the body are not exposed to focused ultrasound or temperature increase, and the drug is safely contained, whilst the liposomes are cleared from the body.

So far,  the Apeikon team has validated the use of their image-guided thermo-sensitive liposomes for drug delivery in several mouse cancer models, providing convincing pre-clinical data (5,6). The next major milestone is to test this technology in human trials, to ensure that the treatment is safe, efficient and to optimise the drug dose for the maximum therapeutic window. Apeikon believes this technology will help patients with solid tumours in several areas of unmet clinical need, such as cancer of the liver, brain and pancreas.

From Academia to Industry

The next few years of Apeikon Therapeutics are set to be challenging, but Dr Thanou and Dr Tadayyon are confident that this is worth the effort.  Particularly as they have put together a fantastic team of scientists, as well as clinical advisors. During our interview they stated that one of the most important elements required to transfer an academic idea to an industrial technology is “the synergy of the team, if you have a good team behind you, they will support you to take the leap.”

We spoke with Dr Thanou about the challenges and barriers she faced as an academic starting a spin-out company. In particular, Maya spoke about the self-doubt that you can feel as an academic. She talked about her co-founder, Moh, as another key element driving the innovation into reality, describing how academia and industry must work ‘hand-in-hand’ to overcome the fear of risk.  

A significant barrier to the commercialisation of an academic discovery is the process of protecting intellectual property. This can be particularly daunting, as academics are not traditionally trained to navigate the patenting process, or taught what innovation actually looks like and how novel a technology must be to patent. Fortunately, Dr Thanou and Dr Tadayyon have significant experience with patenting innovation, and alongside their hard working team they were able to patent their technology early. Both Maya and Moh believe that encouragement to patent innovation should be introduced earlier in academic education.  This, of course, requires total confidence in the science.

Dr Thanou’s confidence in Apeikon Therapeutics comes from the reproducible science that her team has demonstrated. “We have to be 100% sure that the results are going to be absolutely reproducible in the hands of everyone! So, when it was reproducible from the most advanced post-doc to the ‘first time in the lab’ PhD student, then I said – OK, now it’s about time.”

We wish Apeikon Therapeutics the best of luck for the SEC Innovators Club 2021, and we look forward to what the future holds for the company and their innovative 3T technology, in their fight to reduce the side effects while increasing the efficacy of chemotherapy through this advanced patient-centric targeted drug delivery.

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References:

1. Side Effects of Cancer Treatment - National Cancer Institute [Internet]. 2015 [cited 2021 Sep 21]. Available from: https://www.cancer.gov/about-cancer/treatment/side-effects

2. Chemotherapy Side Effects [Internet]. [cited 2021 Sep 21]. Available from: https://www.cancer.org/treatment/treatments-and-side-effects/treatment-types/chemotherapy/chemotherapy-side-effects.html

3. Allen TM, Cullis PR. Liposomal drug delivery systems: From concept to clinical applications. Advanced Drug Delivery Reviews. 2013 Jan 1;65(1):36–48.

4. Magnetic Resonance Imaging (MRI) [Internet]. [cited 2021 Sep 28]. Available from: https://www.nibib.nih.gov/science-education/science-topics/magnetic-resonance-imaging-mri

5. Centelles MN, Wright M, So P-W, Amrahli M, Xu XY, Stebbing J, et al. Image-guided thermosensitive liposomes for focused ultrasound drug delivery: Using NIRF-labelled lipids and topotecan to visualise the effects of hyperthermia in tumours. Journal of Controlled Release. 2018 Jun 28;280:87–98.

6. Cressey P, Amrahli M, So P-W, Gedroyc W, Wright M, Thanou M. Image-guided thermosensitive liposomes for focused ultrasound enhanced co-delivery of carboplatin and SN-38 against triple negative breast cancer in mice. Biomaterials. 2021 Apr 1;271:120758.

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